Container for the aseptic transfer of a biopharmaceutical product

ABSTRACT

A container for ensuring the transport and the aseptic transfer of a biopharmaceutical product from or to a closed chamber provided with a leaktight joining device, includes: an annular flange delimiting an opening, a removable cover, built-in elements for locking/unlocking the removable cover and a peripheral envelope. The built-in locking/unlocking elements include a built-in functional locking/unlocking arrangement formed by a through-housing formed in the annular flange and a blind housing formed in the removable cover, and by a pin at an inner radial position and a pin at an outer radial position. The container is capable of being in an initial locking position, in an intermediate unlocking position and in a final locking position owing to the displacements of the pin at an inner radial position and the pin at an outer radial position in the blind hole of the removable cover and in the through-housing of the annular flange.

The invention relates to the field of the aseptic transfer ofbiopharmaceutical products between a container and a closed chamber.

More specifically, a first aspect of the invention concerns a containerspecially designed for the transport and the aseptic transfer of abiopharmaceutical product from or to an closed chamber. The inventionalso relates, in a second aspect, to an assembly comprising such acontainer, a closed chamber, and a leaktight joining device to ensurethe aseptic transfer of biopharmaceutical products between the containerand the closed chamber. The invention further relates, in a thirdaspect, to a method for the aseptic transfer of a biopharmaceuticalproduct between the container and the closed chamber.

The term biopharmaceutical product or biopharmacy product is understoodhere to mean a product which is related to biotechnology, pharmacy, andmore generally to the medical field. In particular, a biopharmaceuticalproduct is a product obtained from biotechnology—culture media, cellcultures, buffers, artificial nutrition liquids—or a product intended tobe used in the pharmaceutical or medical field, at least in part, as asolid more or less finely divided, as a liquid, or as a paste, or, moregenerally, a physical product—cap, container, integrated ports or tube,syringe, syringe plunger, functional processing or packaging means, amore or less complex assembly comprising a plurality of products,etc.—intended be used inside the closed chamber.

By convention, the terms “container” or “containing” mean that which, inbiopharmacy, is able to and is designed for containing, enclosing, orholding in its interior a specific biopharmaceutical content or whereappropriate several biopharmaceutical contents, in a static manner thatis more or less lasting or permanent. Such biopharmaceutical contentstypically consist of one or more biopharmaceutical product(s) as definedabove. Such containers may be rigid or flexible, reusable or disposable,of various sizes, and are for example bags, sleeves, containers,vessels, bioreactors, or spouts for biopharmaceutical use, although thisis not an exhaustive list.

In the field of aseptic transfers of biopharmaceutical products, thereis a need for establishing a connection between a container and afluid-tight chamber, in particular for the transfer of biopharmaceuticalproducts, without breaking the seal of the container and/or chamberrelative to the outside as this could result in contamination of thebiopharmaceutical products.

To do this, disclosed in the prior art document EP-A1-0688020—in thepreamble of Claim 1—is a container comprising an annular flange definingan opening, a removable door capable of sealing the flange, and built-inmeans for locking/unlocking the removable door against the flange,controlled by actuating means on a leaktight joining device associatedtherewith.

More specifically, the built-in locking/unlocking means comprise,firstly, a first arrangement formed by a through-hole passing throughthe flange and a blind hole extending within the thickness of theremovable door and in line with the through-hole, as well as an internalpin and an external pin engaged one behind the other in these two holes.In this way, the container can change from an initial locking positionwhere the internal pin is engaged with both the flange and the removabledoor, to an intermediate unlocking position where the ends of theinternal and external pins facing each other are placed at the interfaceof the flange and the removable door, which allows separating theremovable door from the flange.

The built-in locking/unlocking means comprise, secondly, a secondarrangement that is structurally and functionally independent of thefirst, consisting of another through-hole passing through the flange,another blind hole extending within the thickness of the removable doorand in line with the through-hole, as well as a pin engaged with thethrough-hole. The pin in question has a length that is greater than thatof the through-hole so that it can be slid inside the blind hole toirreversibly lock the removable door on the annular flange.

This technical solution solves the general problem described above, tothe extent that, when associated with the corresponding joining device,it allows the aseptic transfer of biopharmaceutical products between theclosed chamber and the container. However, this implementation has anumber of disadvantages.

First, the construction of two separate arrangements each comprising athrough-hole in the annular flange to allow transitioning to theintermediate unlocked position and to the final locking positionmultiplies the areas of risk. By their very nature, the through-holes inthe annular flange can be in contact with the environment outside thechamber and can be in contact with the environment inside the chamber. Adefect in manufacturing or in the dimensions of the through-holes orassociated pins can result in a loss of integrity leading tocontamination of the biopharmaceutical products and/or the environmentinside the closed chamber. This unreliability is admittedly limited butcannot be overlooked given the constraints of the field ofbiopharmaceutics.

In addition, this increase in the number of through-holes in the flangeincreases its bulk within the container structure, generates additionalproduction costs, and complicates upgrading the handling systems toautomated solutions that would improve the reliability of these systems.

Furthermore, the justification for this technical solution was that ituses a joining device equipped with a manual lever with two differentdirections of rotation for placing it in the intermediate unlockingposition and the final locking position. Originally, such a technicalsolution facilitated the handling operations for operators since itallowed them first to move the lever in one direction to a stopposition, for placing the container in the intermediate unlockingposition, then to move it in the opposite direction to another stopposition, for the final locking position. However, it has becomeapparent with use that this sequence of operations, combined with theuse of an independent clamping system, was complex and not veryintuitive and thus prone to errors.

Also known from the prior art of document EP-A1-1141974 is a containercomprising built-in locking/unlocking means for the removable coverwhich, as is expressly stated in said document, are similar to thosedisclosed in document FR-A-2721289.

Firstly, the built-in locking/unlocking means allow unlocking theremovable cover from the container by inserting two pins into coaxialholes made in the flange and the removable cover, until the contact areabetween these pins reaches the boundary between the through-holearranged in the flange, and the blind hole made in the removable cover.Secondly, these built-in locking/unlocking means then lock the removablecover on the container by inserting another pin into other coaxial holesmade in the flange and the removable cover.

Because of this similarity, the technical problems mentioned above areencountered in the same manner in the implementation and use of thiscontainer, and there is no need to describe them again.

Also known from the prior art of document WO-A1-2010/054031 is acontainer comprising an annular flange defining an opening, a removablecover capable of sealing the flange, and built-in means forlocking/unlocking the removable cover against the flange, controlled byreversible actuating means carried directly on the container.

More specifically, the built-in locking/unlocking means are formed byseveral arrangements, each comprising a through-hole in the flange, ablind hole made in the removable cover, a pin able to enter through thethrough-hole in the flange and into the blind hole of the removablecover, and a lever able to control the movement of the pin in areversible manner. The container is thus capable of offering only twoalternative positions. In the first position, the locking position,where the removable cover is locked against the flange, the lever islifted so that the pin simultaneously enters the through-hole in theflange and the blind hole of the removable cover, and the cover thenforms a seal against the flange. In the second position, the unlockingposition, where the cover is released, the lever is lowered so that thepin no longer passes beyond the through-hole of the flange which thusreleases the removable cover from the flange.

This technical solution is different from those mentioned in documentsEP-A1-1141974 and FR-A-2721289, in that it allows the operators tochange the container in a reversible manner from a locking position toan unlocking position simply by manipulating levers arranged on theflange of the container. The container is thus reusable.

However, this arrangement also has disadvantages.

Due to the reversibility of the locking/unlocking and the accessibilityof the actuating means—namely the levers—mounted directly on the flangeof the container, the risk of unintentionally or accidentally openingcontainers filled with biopharmaceutical products is considerablyincreased. It is also possible for such containers to be initially open,thereby compromising the isolation of the biopharmaceutical productsrelative to the outside, as they are then closed and this breach in thecontainment cannot be identified.

Document WO2010/054031 discloses a container intended for the aseptictransfer of a product to a chamber. The container comprises an annularflange defining an opening and there is a removable cover provided.

Document GB 2,102,719 discloses a system for bringing hazardousmaterials in and out of an enclosure, such as a glovebox, through a portin a wall of the enclosure. The port is normally closed by a door whichcooperates with a removable end closure on a container or the like whenthe latter is presented to and secured at the port. The container issecured in position at the port by means of a rotatable coupling ring. Alocking device ensures that the door cannot be opened in the absence ofa container at the port and also that the container cannot be removedfrom the port when the door is open. In place of the container, a glovesecured to a rigid sleeve may be used to allow the operator to perform awork function within the glovebox.

Document FR 2872446 discloses a double-door leaktight transfer devicefor providing a fluid-tight seal between a first sealed chamber, forexample a containment cell, and a second sealed chamber, for example atransfer box, comprising two doors each equipped with locking means forlocking it to a flange having a central opening and an actuator foractuating the locking means, the actuators being rotatably mounted inthe doors and comprising a peephole.

EP 0688020 discloses a leaktight joining device between two chambersisolated from an external environment and each equipped with a doorcapable of sealing an opening of the corresponding chamber delimited byan annular flange, each door being defined with an inside face incontact with the interior of the chamber and an outside face in contactwith said external environment, said doors being provided withcooperating assembly means which allow applying them one against theother to create a seal, in order to mutually isolate their outsidefaces, wherein one of the two chambers is of the disposable type andcomprises final locking means for its own door, controlled by firstactuating means installed on the other chamber.

GB 2 218 663 discloses a double-lidded system comprising a firstcylindrical container, open at one end, a first lid for the firstcontainer, means defining a port for a second container, and a secondlid for said port, the first container having a peripheral seal forsealing to the port and to the first lid, and the second lid having aperipheral seal for sealing to the port and the first lid, wherein thefirst lid comprises a catch mechanism of a first rotary element forsecuring the first lid to the first container, the first containerincorporating engagement means for cooperating with the catch mechanismof the first rotary element, the second lid incorporates a rotary driveshaft extending through it and means for rotating the shaft areprovided, and a catch mechanism of the second rotary element which canbe actuated by the shaft to secure the first lid to the second lid, thefirst lid comprising means with which the catch mechanism of the secondrotary member can engage, the system lastly incorporating a clutch teethmechanism with at least twenty teeth which are engaged when the firstlid is adjacent to the second lid such that rotation of the shaft causessimultaneous rotation of the first and second rotary catch mechanisms.

In this context, the aim of the present invention is to provide acontainer specially intended for the transport and aseptic transfer of aproduct belonging to the biopharmaceutical field that is without atleast one of the above limitations.

More particularly, the present invention relates to a container that iscapable of such transfer without breaching its seal and which presents alimited number of at-risk areas, is simple to produce, and is intuitiveto use in order to limit the risk of inadvertent or deliberatecontamination.

For that purpose, a first aspect of the invention relates to a containerspecially designed for the transport and the aseptic transfer of abiopharmaceutical product to or from a closed chamber equipped with aleaktight joining device, comprising: an annular flange delimiting anopening; a removable cover adapted for sealing the opening of theannular flange; built-in means for locking/unlocking the removable coveron the annular flange; and a peripheral envelope integral with theannular flange and delimiting an enclosed inside space adapted forreceiving products belonging to the biopharmaceutical field; wherein thebuilt-in locking/unlocking means comprise at least one built-infunctional locking/unlocking arrangement formed, on the one hand, by athrough-housing formed in the annular flange and a blind housing formedin the removable cover and in the extension of the through-housing whenthe removable cover seals the opening of the annular flange, and, on theother hand, by a pin at an inner radial position and a pin at an outerradial position which can be introduced and moved within the blindhousing of the removable cover and the through-housing of the annularflange; the container being able to be in an initial locking positionwhere, on the one hand, the pin at an inner radial position has aninternal functional portion for initial locking arranged in the blindhousing of the removable cover and a external functional portion forinitial locking arranged in the through-housing of the annular flange soas to prevent the relative movement of the removable cover with respectto the annular flange, and, on the other hand, the pin at an outerradial position is at least partially arranged in the through-housing ofthe annular flange; the container being able to be in an intermediateunlocking position in which, on the one hand, the pin at an inner radialposition is at least partially arranged in the blind housing of theremovable cover and is completely outside the through-housing of theannular flange, and, on the other hand, the pin at an outer radialposition is at least partially arranged in the through-housing of theannular flange and is completely outside the blind housing of theremovable cover so as to allow the relative movement of the removablecover with respect to the annular flange. More particularly, thecontainer is characterized by its being able to be in a final lockingposition where, on the one hand, the pin at an inner radial position isarranged in the blind housing of the removable cover, and, on the otherhand, the pin at an outer radial position has an internal functionalportion for final locking arranged in the blind housing of the removablecover and an external functional portion for final locking arranged inthe through-housing of the annular flange so as to prevent the relativemovement of the removable cover with respect to the annular flange.

Such an embodiment avoids the use of two separate holes, in the annularflange and in the removable cover, changing to the intermediateunlocking position and to the final locking position. This limits therisk of leakage that can result from manufacturing or dimensionaldefects. Furthermore, the use of built-in functional locking/unlockingarrangements only requiring the movement of the pins along a single axisand in a single direction simplifies the mechanism for actuating thebuilt-in locking/unlocking means, making it more intuitive to use whileat the same time allowing automation of this process.

According to one embodiment, the through-housing and the pin at an outerradial position have lengths such that, when the built-inlocking/unlocking means are in the initial locking position, said pin atan outer radial position has a functional end portion at the outerradial position which is either completely outside the through-housing,or is housed inside the through-housing, or is flush with the outer endopening of the through-housing.

Also according to one embodiment, the through-housing and the pin at anouter radial position have lengths such that, when the built-inlocking/unlocking means are in the intermediate unlocking position, saidpin at an outer radial position has a functional end portion at theouter radial position which is either completely outside thethrough-housing, or is housed inside the through-housing, or is flushwith the outer end opening of the through-housing.

According to one embodiment, in addition, the through-housing and thepin at an outer radial position have lengths such that, when thebuilt-in locking/unlocking means are in the final locking position, saidpin at an outer radial position has a functional end portion at theouter radial position which is either completely outside thethrough-housing, or is housed inside the through-housing, or is flushwith the outer end opening of the through-housing.

The fact that the pin at an outer radial position is completely outsidethe through-housing when the container is in the initial lockingposition or the intermediate unlocking position facilitates theoperation of stationary locking/unlocking means consisting of causingthe container to transition from the initial locking position to theintermediate unlocking position, or from the intermediate unlockingposition to the final locking position. In effect, the pin at an outerradial position thus remains accessible without the radially movablepushing element having to move all the way inside the through-housing.Furthermore, the fact that this pin at an outer radial position is alsocompletely outside the through-housing when the container is in thefinal locking position can be useful when it is necessary to disassembleor reopen the container after it has been placed in the final lockingposition, because the pin at an outer radial position is then moreaccessible than if it were positioned fully within the through-housingin the annular flange.

On the contrary: the fact that the pin at an outer radial position ispositioned fully inside the through-housing when the container is in theinitial locking position, the intermediate unlocking position, or thefinal locking position, allows limiting access to this pin at an outerradial position and therefore makes the inadvertent actuation of thebuilt-in locking/unlocking means less probable and more complex. Inaddition, the transition to the final locking position becomes virtuallyirreversible. This option is advantageous, particularly when thecontainer is disposable.

In addition, using the pin at an outer radial position so that it isflush with the outer end of the through-housing—in any of the initiallocking, intermediate unlocking, or final locking positions—can restrictthe introduction of stationary unlocking or locking means deep insidethe through-housing while limiting access to this pin at an outer radialposition, which reduces the risk of inadvertently opening the container.

In one embodiment, the pin at an inner radial position and the pin at anouter radial position have substantially identical lengths. Thissimplifies the procurement, production, and assembly of the inner andouter pins as it is then no longer necessary to distinguish the pins bytheir respective dimensions.

In one embodiment, the through-housing, the blind housing, the pin at aninner radial position, and the pin at an outer radial position arecoaxial and oriented in a radial direction relative to the annularflange.

In an alternative embodiment, the blind housing, the pin at an innerradial position, and the pin at an outer radial position are coaxial andoriented in a direction forming an angle a with respect to a radialdirection relative to the annular flange.

Moreover, according to one embodiment, the container also comprisesbuilt-in isolation and protection means arranged on an outer peripheraledge of the annular flange so as to obstruct the inadvertentmanipulation of the built-in locking/unlocking means. These means canthus reduce the risk of inadvertent manipulation which could cause thecontainer to transition from its initial locking position to theintermediate unlocking position, particularly during transport.

In this case, according to one embodiment, the built-in isolation andprotection means comprise at least one built-in functional arrangementfor isolation and protection, provided around the through-housing so asto obstruct the inadvertent manipulation of the pin at an outer radialposition.

Thus, according to one embodiment, the built-in functional arrangementfor isolation and protection has radial dimensions such that, in atemporary locking position, the pin at an outer radial position does notextend beyond said isolation and protection means.

In one embodiment, the built-in functional arrangement for isolation andprotection comprises at least one lug, preferably two lugs, arrangedaround the through-housing of the annular flange.

In an alternative or additional embodiment, the isolation and protectionarrangement may also comprise a bore formed in the annular flange andhaving a diameter greater than the diameter of the through-housing. Thismakes it more difficult to access the pin at an outer radial positionbut does not further complicate the movement of the latter by thestationary locking and unlocking means.

In one embodiment, the container further comprises built-in temporaryclamping means arranged on an outer peripheral edge of the annularflange so as to allow temporarily clamping the container by preventingits axial movement on the closed chamber via actuation of the leaktightjoining device.

In this case, according to one embodiment, the built-in temporaryclamping means comprise at least one built-in functional arrangement fortemporary clamping formed by at least one lug, preferably two lugs,having a built-in functional surface for axial clamping adapted to abutagainst a stationary functional surface for axial clamping, of theleaktight joining device, so as to prevent axial movement of thecontainer relative to the closed chamber.

Furthermore, according to one embodiment, the built-in temporaryclamping means are at least partly formed by the isolation andprotection means, thereby simplifying and reducing the materialsrequired for the container while lowering production costs.

In one embodiment, the built-in functional arrangement for temporaryclamping and the built-in functional arrangement for isolation andprotection are formed by at least one common lug, and preferably twocommon lugs.

In one embodiment, the built-in locking/unlocking means comprises nbuilt-in functional arrangements for locking/unlocking, regularlydistributed around the annular flange and the removable cover, with ngreater than or equal to 1. This reinforces the initial and finallocking of the removable cover against the annular flange.

In this case, according to one embodiment, the built-in isolation andprotection means comprise n built-in functional arrangements forisolation and protection, regularly distributed around the annularflange and indexed relative to the n built-in functional arrangementsfor locking/unlocking.

In one embodiment, the built-in temporary clamping means comprise mbuilt-in functional arrangements for temporary clamping, regularlydistributed around the annular flange, with m greater than or equal to1.

In this case, according to one embodiment, n is equal to m and thebuilt-in functional arrangements for temporary clamping are indexedrelative to the built-in functional arrangements for locking/unlocking.

In one embodiment, the container is disposable.

The invention also relates, in a second aspect, to an assemblycomprising a chamber, a leaktight joining device, and a container asdescribed above, for performing the aseptic transfer of abiopharmaceutical product between the chamber and the container.

In one embodiment, the chamber comprises a peripheral wall in which isarranged an opening sealed by a removable door, and the leaktightjoining device comprises: stationary temporary clamping means able tokeep the container clamped against the chamber so that the removablecover of said container is sealingly held against the door of saidchamber; stationary unlocking means able to cause the container totransition from an initial locking position where the removable coverseals the container to an intermediate unlocking position where theremovable cover is disengaged from the container and is sealingly heldagainst the door of the chamber so as to ensure an aseptic communicationbetween said container and said chamber; stationary locking means ableto cause the container to transition from the intermediate unlockingposition to a final locking position where said removable cover onceagain seals the container; an annular functional ring gear able torotate about a geometric axis of rotation so as to actuate thestationary unlocking means and the stationary locking means of thecontainer; the stationary temporary clamping means, the stationaryunlocking means, and the stationary locking means being mechanicallylinked to the annular functional ring gear so that the one-way rotationof said annular functional ring gear about the geometric axis ofrotation successively causes the actuation of the stationary temporaryclamping means to hold the container in position against the chamber,then the actuation of the stationary unlocking means which causes thecontainer to transition to the intermediate unlocking position, then theactuation of the stationary locking means of the container which causesthe container to transition to the final locking position, and theactuation of the stationary temporary clamping means of the containerwhich results in the release of the container.

Furthermore, according to a third aspect, the invention relates to amethod for aseptic transfer intended to ensure the aseptic transfer of abiopharmaceutical product between a container and a chamber which arepart of an assembly as described above, and comprises the successivesteps of: having available the chamber, the leaktight joining device,and the container; positioning the container against the peripheral wallof the chamber; generating an axial clamping of the annular flange ofthe container against the peripheral wall of the chamber by one-wayrotation of the annular functional ring gear; generating the transitionof the container from the initial locking position to the intermediateunlocking position by one-way rotation of the annular functional ringgear, causing the movement of the pins at the inner and outer radialpositions within the through-housing and blind housing; simultaneouslyopening the removable door of the chamber and the removable cover of thecontainer, the removable cover being sealingly attached against theremovable door; aseptically transferring one or more biopharmaceuticalproduct(s) between the container and the chamber; simultaneously closingthe removable door of the chamber and the removable cover of thecontainer, the removable cover being sealingly attached against theremovable door; generating the transition of the container from theintermediate unlocking position to the final locking position by one-wayrotation of the annular functional ring gear which causes movement ofthe pins at the inner and outer radial positions within thethrough-housing and blind housing; generating the axial unclamping ofthe annular flange of the container relative to the peripheral wall ofthe chamber by one-way rotation of the annular functional ring gear.

Other features and advantages of the invention will become apparent fromthe description which is given below for informational purposes andwhich is non-limiting, with reference to the accompanying drawings,where:

FIG. 1 is a general overview, showing an exploded perspective view of anembodiment of a leaktight joining device associated with the peripheralwall of a chamber;

FIGS. 2 a and 2 b are two general perspective views, from inside thechamber and from outside the chamber, of the leaktight joining device ofFIG. 1 installed on a portion of the peripheral wall of the chamber andready to be associated with the annular flange of a container accordingto the invention;

FIGS. 3 a and 3 b are two perspective detail views of the annularfunctional ring gear that is part of the embodiment of the joiningdevice of FIG. 1;

FIG. 4 is a general overview, showing an exploded perspective view of anembodiment of a container according to the invention where theperipheral envelope is not shown;

FIG. 5 a is a cross-sectional detail view, showing a portion of thecontainer of FIG. 4 in an initial locking position;

FIG. 5 b is a cross-sectional detail view, showing a portion of thecontainer of FIG. 4 in an intermediate unlocking position;

FIG. 5 c is a cross-sectional detail view, showing a portion of thecontainer of FIG. 4 in a final locking position;

FIG. 6 is a cross-sectional detailed representation of an assemblycomprising a closed chamber, a leaktight joining device, and a containeraccording to the invention associated with the leaktight joining deviceand in the initial locking position.

FIG. 1 shows a closed chamber 10 comprising a peripheral wall 12defining an enclosed inside space 14 and a circular opening 16 allowingthe introduction of biopharmaceutical products (not shown) into theenclosed inside space 14.

The chamber 10—which can be an enclosed area or other analogoussystem—is designed to be permanently isolated from the outsideenvironment. Thus, to avoid any loss of integrity and to maintain anaseptic environment within the inside space 14, the annular opening 16is sealed by a removable door 18 positioned in the inside space and ableto move from a closed position where the circular opening 16 isobstructed to an open position where the circular opening 16 is nolonger obstructed.

By convention, the terms “internal” and “external” or “inner” and“outer” are used in the rest of this document to describe the relativepositions of objects with respect to the geometric axis of the annularopening 16. Thus, objects described as “internal” or having an “innerradial position” should be regarded as positioned closest to thegeometric axis of the annular opening 16, while objects described as“external” or having an “outer radial position” are to be considered aspositioned farthest from the geometric axis of the annular opening 16.

FIGS. 2 a and 2 b show a container 20 intended for transportingbiopharmaceutical products and ready to be associated with the closedchamber 10 in order to perform an aseptic transfer of biopharmaceuticalproducts to or from the chamber 10.

For this purpose, the container 20 comprises a peripheral envelope (notshown) defining an enclosed inside space 24 into which thebiopharmaceutical products can be introduced. The peripheral envelopealso includes an annular opening 26 delimited by an annular flange 30 towhich the peripheral envelope is integrally attached. The container 20further comprises a removable cover 28 capable of sealing the opening 24of the annular flange 30 by resting on a seal 22.

The container 20 can be realized according to different embodiments and,therefore, can have a peripheral envelope that is flexible and intendedfor a single use or rigid and intended to be reused after adecontamination procedure well known to those skilled in the art.

FIGS. 1, 2 a and 2 b illustrate an embodiment of a leaktight joiningdevice 40.

This leaktight joining device 40 is intended to allow the aseptictransfer of biopharmaceutical products from the container 20 (describedbelow) to the chamber 10. The object of the leaktight joining device 40is therefore firstly to allow the assembly of the chamber 10 and thecontainer 20, and then to allow placing the inside space 14 of thischamber 10 in temporary communication with the inside space of thiscontainer 20 in order to transfer biopharmaceutical products from one tothe other, and lastly, to ensure the separation of said chamber 10 andsaid container 20.

These successive steps—encompassed below under the descriptor “aseptictransfer”—must be carried out without any communication between theoutside environment and the inside spaces 14, 24 of the chamber 10 andof the container 20.

To do this, the leaktight joining device 40 according to the embodimentof FIG. 1 has a part formed outside the chamber 10 and supported by theperipheral wall 12—or by a supporting part distinct from the peripheralwall 12 but immovably attached to it—facing the annular opening 16. Morespecifically, the leaktight joining device 40 comprises an annularfunctional ring gear 42 having a face 42 a oriented towards theperipheral wall 12 of the chamber 10 and a face 42 b oriented towardsthe outside environment.

The annular functional ring gear 42 also has an inner peripheral edge 44_(INT) and an outer peripheral edge 44 _(EXT) inscribed within threetrack rollers 46 which are supported by the external face of theperipheral wall 12. The annular functional ring gear 42 is thuspositioned outside the chamber 10, which facilitates any maintenanceoperations. The three track rollers 46 form a track for the annularfunctional ring gear, and allow it to rotate about the geometric axis ofthe annular opening 16. It should be stressed, however, that theposition of the annular functional ring gear could be maintained by someother similar mechanical element (bearing, etc.).

In the embodiment of FIG. 1, the annular functional ring gear 42, whichpresents several portions having different mechanical functions(described below), is formed as a single part—by machining, molding, orsimilar—from a single block of material. This embodiment has theadvantage of simplifying the production of the annular functional ringgear, simultaneously reducing the production costs, and ensuring optimumpositioning of the functional surfaces of the annular functional ringgear 42. However, it is understood that in other embodiments the annularfunctional ring gear may be formed from a plurality of discretemechanical parts assembled together into one piece so that rotation ofone of these mechanical parts around the geometric axis of rotation Rcauses the rotation of the whole.

It should be noted that, by convention, objects referred to as“stationary” are part of the leaktight joining device 40 and aretherefore intended to be connected and permanently attached to thechamber 10. Conversely, objects referred to as “built-in” are intendedto be supported by the containers 20 and therefore move with saidcontainers.

The annular functional ring gear 42, more particularly illustrated inFIGS. 3 a and 3 b, has a stationary rotary drive portion 48 arrangednear the outer peripheral edge of the annular functional ring gear 42and formed by radially oriented teeth 48 a driven by a motor 48 b,placed outside the chamber 10, or in an alternative embodiment, by amanually actuated lever (not shown). From the momentum of the motor 48b, the annular functional ring gear is able to begin a one-way rotationabout the geometric axis of rotation R. By convention, the one-wayrotation is considered below to be clockwise. However, the direction ofrotation of the annular functional ring gear can alternativelycorrespond to the counterclockwise direction.

The leaktight joining device 40 comprises stationary temporary clampingmeans 50.

The stationary temporary clamping means 50 serve to keep the container20 clamped against the chamber 10 so that the removable cover 28 of thecontainer 20 is sealingly applied against the removable door 18 of thechamber 10.

These stationary temporary clamping means 50 are mechanically linked tothe annular functional ring gear 42 so that the rotation of this annularfunctional ring gear 42 about the geometric axis of rotation R in theclockwise direction mechanically actuates the stationary temporaryclamping means 50.

In the embodiment of FIG. 1, the stationary temporary clamping means 50comprise four stationary functional arrangements for temporary clamping52 regularly distributed around the annular functional ring gear 42.Each of these stationary functional arrangements for temporary clamping52 is formed of a functional clamping ring portion 54 which is part ofthe annular ring 42. Each functional clamping ring portion 54 thus has afunctional surface for axial clamping 56, and an opening 58 forinserting complementary built-in clamping means arranged on a portion ofthe outer periphery of the container (described later).

In the embodiment of FIG. 1, the functional surface for axial clamping56 is formed on the inner peripheral edge 44 _(INT) of the annularfunctional ring gear 42 by an axially offset extension of the outer faceof the peripheral wall 12 of the chamber 10, with regular interruptionsforming the insertion opening 58. However, alternative embodiments foraxially clamping the annular flange 30 of the container 20 against theouter face of the peripheral wall 12 of the chamber 10 could also beconsidered.

The leaktight joining device 40 comprises stationary unlocking means 60.

The stationary unlocking means 60 are intended for allowing thecontainer 20 to transition from an initial locking position where theremovable cover 28 seals the container 20, to an intermediate unlockingposition where the removable cover 28 is detached from the container andsealingly applied against the door 18 of the chamber 10 so as to ensurean aseptic communication between the container 20 and the chamber 10.

As before, these stationary unlocking means 60 are mechanically linkedto the annular functional ring gear 42 so that the clockwise rotation ofthis annular functional ring gear 42 about the geometric axis ofrotation R mechanically actuates the unlocking means 60. However, inview of the arrangement of these stationary unlocking means 60 relativeto the stationary temporary clamping means 50, the actuation of thestationary unlocking means 60 only occurs after the axial clamping ofthe container 20 against the chamber 10.

According to the embodiment of FIG. 1, also visible in FIGS. 3 a and 3b, the stationary unlocking means 60 comprise several stationaryfunctional unlocking arrangements 62—in this case fourarrangements—regularly distributed around the annular functional ringgear 42.

Each of these stationary functional unlocking arrangements 62 firstlycomprises a functional ring portion forming an inward- or outward-facingradial cam 64 which is part of the annular functional ring gear 42. Inthis case, the functional ring portion forming the radial cam 64 iscreated using a guideway 66 created in the annular functional ring gear42 although this embodiment is not limiting.

Each of these stationary functional unlocking arrangements 62 secondlycomprises a radially movable pushing element 68 able to cooperate withthe functional ring portion forming the radial cam 64. In this way,during the rotation of the functional ring gear 42 to an intermediateunlocking position, the relative movement of the annular functional ringgear 42 with respect to the pushing element 68—which remainsrotationally fixed as it is locked in a complementary arrangement68′—causes movement of said pushing element 68 in the radial directionand causes the container 20 to transition from an initial lockingposition to an intermediate unlocking position (described later).

More particularly, according to the illustrative and non-limitingembodiment of FIG. 1, the pushing element 68 which is rotationally fixedrelative to the peripheral wall 12 of the chamber 10, has in particulara roller 68 a arranged in the guideway 66 and an activation pin 68 bconnected to the roller 68 a so that the movement of this roller in theradial direction causes a radial movement of the activation pin 68 b,until the container 20 transitions to the intermediate unlockingposition.

It should be noted that the above phrase “movement in the radialdirection” should be understood in its most general sense and can thuscorrespond to a line passing through the geometric axis of rotation R orslightly inclined and forming an angle a relative to the radialdirection of the annular flange 30.

The leaktight joining device 40 comprises stationary locking means 70.

The stationary locking means 70 are intended for causing the container20 to transition from the intermediate unlocking position to a finallocking position where said removable cover 28 again seals the container20.

As before, the stationary locking means 70 are mechanically linked tothe annular functional ring gear 42 so that the clockwise rotation ofthis annular functional ring gear 42 about the geometric axis ofrotation R mechanically actuates the stationary locking means 70.Similarly to the above, the relative position of the stationary lockingmeans 70 and the stationary unlocking means 60 around the annularfunctional ring gear 42 is such that the actuation of these stationarylocking means 70 can only occur after the stationary unlocking means 60are stopped.

According to the embodiment of FIG. 1, visible in FIGS. 3 a and 3 b, thestationary locking means 70 comprise four stationary functionalunlocking arrangements 72 regularly distributed around the annularfunctional ring gear 42.

Each of these stationary functional unlocking arrangements 72 firstlyincludes a functional ring portion forming an inward- or outward-facingradial cam 74 which is part of the annular functional ring gear 42. Asbefore, this functional ring portion forming a radial cam 74 is based ona guideway 76 formed in the annular functional ring gear 42, althoughthis embodiment is not limiting.

Each of these stationary functional unlocking arrangements 72 thencomprises a radially movable pushing element 78, able to cooperate withthe functional ring portion forming a radial cam 74. In this manner,when the functional ring gear 42 is rotated to a final locking position,the relative movement of the annular functional ring gear 42 withrespect to the pushing element 78—which remains rotationally fixedbecause it is locked in a complementary arrangement 68′—causes saidpushing element 78 to be moved in the radial direction and causes thecontainer 20 to transition from the intermediate unlocking position to afinal locking position (described below).

More particularly, according to the illustrative and non-limitingembodiment of FIG. 1, the pushing element 78 which is rotationally fixedrelative to the peripheral wall 12 of the chamber 10 is the same as thepushing element 68 which is part of the stationary functional unlockingmeans 60. This pushing element 78 therefore comprises a roller 68 aarranged in the guideway 76 and an activation pin 68 b connected to theroller 68 a so that the movement of said roller in the radial directioncauses a radial movement of the activation pin 68 b, until the container20 is transitioned to the intermediate unlocking position.

It therefore follows that the functional ring portion forming a radialcam 74 of the stationary functional locking arrangement 72, is arrangedin the extension of the functional ring portion forming a radial cam 64of the stationary functional unlocking arrangement 62, considering theone-way rotation of the annular functional ring gear 42. In this regard,the ring portions forming a radial cam 72, 62 of the stationaryfunctional locking arrangement 74 and of the stationary functionalunlocking arrangement 62 are formed by a continuous guideway 66, 76arranged in the annular functional ring gear 42, and the radiallymovable pushing element 68, 78 comprises a roller 68a arranged in thecontinuous guideway 66, 76 such that the rotation of the annularfunctional ring gear generates radial movement of the roller 68 a whichresults in the corresponding displacement of an activation pin 38 b.

Conversely, according to one alternative (not shown), the stationaryunlocking means 60 and the stationary locking means 70 may optionally bestructurally and functionally separate and independent of each other.

The leaktight joining device 40 comprises stationary retention/releasemeans 80.

These stationary retention/release means 80 are intended todisable/enable the opening of the removable door 18 of the chamber 10and are mechanically connected to the annular functional ring gear 42such that the clockwise one-way rotation of this annular functional ringgear 42 about the geometric axis of rotation R mechanically actuates thestationary retention/release means 80. More particularly, because of theposition of these stationary retention/release means 80 on the annularfunctional ring gear 42, these means ensure the release of the removabledoor 18 from the chamber 10. In the embodiment of FIG. 1, the stationaryretention/release means 80 ensure the release of the removable door 18after actuation of the stationary unlocking means 60 has caused thecontainer 20 to transition to the intermediate unlocking position. Inthis manner, opening the removable door 18 of the chamber 10 is delayedindefinitely when a problem occurs during the intermediate unlocking ofthe container 20. This minimizes containment issues—which arenecessarily more complex to rectify within the chamber 10—which couldresult from improper handling of the container 20. Similarly, thesestationary retention/release means 80 are arranged on the annularfunctional ring gear 42 to ensure that the removable door 18 of thechamber 10 remains in place until the stationary locking means 70 havebeen activated in order to transition the container 20 to the finallocking position.

According to another embodiment, it is also possible to arrange thestationary retention/release means 80 on the annular functional ringgear 42 so that these means release the removable door 18 simultaneouslywith the transition of the container 20 to the intermediate unlockingposition, then block this removable door 18 simultaneously with thetransition of the container 20 to the final locking position.

Finally, according to a third embodiment, it is conceivable to arrangethe stationary retention/release means 80 on the annular functional ringgear 42 so that these means release the removable door 18 of the chamber10 before the container 20 transitions to the intermediate unlockingposition, and these means block the removable door 18 of the chamber 10after the container 20 transitions to the final locking position.

The stationary retention/release means 80 as illustrated in FIG. 1comprise at least one stationary functional arrangement forretention/release 82 formed by a functional ring portion forming gearteeth 84 which is part of the annular functional ring gear 42. As such,this functional ring portion forming gear teeth 84 is positioned outsidethe chamber 10.

Furthermore, in the embodiment of FIG. 1, this functional ring portionforming gear teeth 84 is notched so as to engage with a drive shaft 86passing through the peripheral wall 12 of the chamber 10 and whichdrives a blocking member 88 during the one-way rotation of thefunctional ring gear. More particularly, the blocking member 88—which islocated within the inside space 14 of the chamber 10—is arranged to beable to move from a blocked position where a covering portion 88 aprevents the removable door 18 of the chamber 10 from opening, to afreed position where the covering portion 88 a no longer prevents theremovable door 18 from opening.

The leaktight joining device 40 also comprises stationary operatingmeans 90.

These stationary operating means 90 are intended for opening theremovable door 18 of the chamber 10 and for sealing it closed again.

To do this, the stationary operating means 90 may, according to a firstembodiment (not shown), be driven mechanically by the annular functionalring gear 42. In this case, the stationary operating means 90 aremechanically connected to the annular functional ring gear 42 so thatthe clockwise one-way rotation of the annular functional ring gear 42about the geometric axis of rotation R mechanically actuates thestationary operating means 90. More particularly, the position of thesestationary operating means 90 on the annular functional ring gear 42allows opening the removable door 18 of the chamber 10 after thecontainer 20 transitions to the unlocking position, then closing theremovable door 18 before the container 20 transitions to the finallocking position.

In a second embodiment illustrated by FIG. 1, the stationary operatingmeans 90 are driven by a motor 92 controlled by the displacement of theannular functional ring gear 42.

These stationary operating means 90 then comprise a rotational arm 94adapted to rotate about a horizontal axis of rotation, as well as atranslational arm 96 adapted to move along a horizontal axis. In thismanner, the stationary operating means 90 allow, by means of the motor92, moving the removable door 18 of the chamber 10, first in an axialdirection, then in a direction substantially perpendicular to the axialdirection so that the removable door 18 does not interfere with thepassage of the biopharmaceutical product during the aseptic transferbetween the chamber 10 and the container 20.

It should be noted that, according to the invention, the temporarystationary clamping means 50, the stationary unlocking means 60, thestationary locking means 70, and possibly the retention/release means 80and the operating means 90, are mechanically linked to the annularfunctional ring gear 42 and arranged so that the clockwise one-wayrotation of said annular functional ring gear 42 about the geometricaxis of rotation R successively causes the actuation of the temporarystationary clamping means 50 to maintain the container 20 in positionagainst the chamber 10, and then simultaneously or successively theactuation of the stationary unlocking means 60 which ensures thetransition of the container 20 to the intermediate unlocking positionand the actuation of the stationary retention/release means 80 whichensures the release of the removable door 18 of the chamber 10, thensimultaneously or successively the actuation of the stationaryretention/release means 80 which blocks the removable door 18 of thechamber 10 and the actuation of the stationary locking means 70 whichensures the transition of the container 20 to the final lockingposition, and once again the actuation of the temporary stationaryclamping means 50 for the container in order to release the container20.

Moreover, the temporary stationary clamping means 40 are arranged toensure the positioning of the container 20 and an indexing relative tothe other functional means. Similarly, the accumulation of severalfunctional arrangements on the annular functional ring gear 42 allowscompleting a manipulation cycle of the container 20 with a 1/n rotation.In this current case, the embodiment comprises four distinct functionalarrangements distributed regularly over the annular functional ringgear, but it would be possible to include less—one, two, or three—or toinclude more.

It should be noted that the one-way rotation of the annular functionalring gear 42 ensures the actuation of the temporary stationary clampingmeans, unlocking means, locking means, retention/release means, andoperating means, which this annular functional ring gear moves in onedirection of rotation or in the other.

Moreover, it is also possible to integrate this annular functional ringgear 42, not outside the chamber 10 as shown in the embodiment of FIG. 1but directly in the inside space 14 of the chamber 10, against the innerface of the peripheral wall 12. This embodiment would avoid the use ofretention/release means 80 having a drive shaft 86 passing through theperipheral wall 12.

FIG. 4 shows details of an embodiment of a container intended to beassociated with the leaktight joining device of the invention.

The peripheral envelope of the container 20 is not shown in thisillustration, however.

As indicated above, this container 20 is intended for the transport andaseptic transfer of biopharmaceutical products to or from a chamber 10equipped with the leaktight joining device 40 according to theinvention.

For that purpose, the container 20 comprises the annular flange 30delimiting the annular opening 26, the removable cover 28 adapted forsealing the opening 26 of the annular flange 30, and the peripheralenvelope secured to the annular flange 30 and delimiting the enclosedinside space 24 for containing the biopharmaceutical products. In thismanner, when closed by the removable cover 28, the container 20 issealed, preventing any leakage or any introduction of material into theinside space 24. The container 20 may be rigid or flexible and reusableor disposable, depending on the case. By way of example and in no waylimiting, it may be a container 20 of any size, such as a bag, a sleeve,a vessel, a bioreactor, a spout, etc.

The container 20 also comprises built-in temporary clamping means 100.

These built-in temporary clamping means 100 are arranged on an outerperipheral edge of the annular flange 30 in a manner that allowstemporarily clamping the container 20 by axially locking it in place onthe outside face of the peripheral wall 10 of the chamber 10 via theactuation of the leaktight joining device 40.

More particularly, according to the embodiment of FIG. 4, the built-intemporary clamping means 100 comprise at least a built-in functionalarrangement for temporary clamping 102 formed by at least one lug 104,preferably two lugs 104, having a built-in functional surface for axialclamping 106 adapted to abut against the functional stationary surfacefor axial clamping 56 of the leaktight joining device 40. These lugs104, which can be positioned between the outer face of the peripheralwall 12 of the chamber 10 and the stationary functional surface foraxial clamping 56 of the leaktight joining device 40 by first passingthrough one of the openings 58 for introducing this leaktight joiningdevice 40, allow blocking the axial movement of the container 20relative to the chamber 10.

When the container 20 is clamped against the chamber 10, the removablecover 28 of the container 20 remains sealingly fixed—magnetically or byother means—against the removable door 108 of the chamber 10. In thismanner, the outside space contained between the removable cover 28 andthe removable door 18 cannot leak during the aseptic transfer.

The container 20 also includes built-in locking/unlocking means 110 forholding the removable cover 28 on the annular flange 30.

These built-in locking/unlocking means 110—their structure is detailedbelow—have the function of maintaining the container 20 in threedistinct positions. The first position is referred to as the initiallocking position because the locking/unlocking means 110 preventrelative movement of the removable cover 28 with respect to the annularflange 30. The second position, referred to as the intermediateunlocking position, occurs when the annular flange 30 of the container20 is clamped axially against the peripheral wall 12 of the chamber 10and allows relative movement of the removable cover 28 with respect tothe annular flange 30. The third position, referred to as the finallocking position, is assumed to take place after the aseptic transfer ofbiopharmaceutical products between the container 20 and the chamber 10and prevents, irreversibly or again and reversibly, the relativemovement of the removable cover 28 with respect to the annular flange30.

To ensure this transition from the initial locking position to theintermediate unlocking position and then to the final locking position,the built-in locking/unlocking means 110 according to the embodiment ofFIG. 4 include four built-in functional arrangements forlocking/unlocking 112, regularly distributed around the annular flange28 of the cover 30.

Each built-in functional arrangement for locking/unlocking 112 comprisesa through-housing 114 formed in the annular flange 30 and a blindhousing 116 formed in the removable cover 28 of the container 20 and inthe extension of the through-housing 114.

Each built-in functional arrangement for locking/unlocking 112 alsocomprises a pin at an inner radial position 118 and a pin at an outerradial position 120. In the embodiment of FIG. 4, these two inner 118and outer 120 pins have an elongated cylindrical body allowing them tobe introduced and moved within the blind housing 116 formed in theremovable cover 28 and the through-housing 114 arranged in the annularflange 30. It should be noted that the dimensional characteristics andthe properties of the outer surface of these inner 118 and outer 120pins are such that the pins can only be moved within the blind housing116 and the through-housing 114 by gravity. In addition, these inner 118and outer 120 pins could have a different body shape—for example,parallelepipedal—to achieve the same result.

In the embodiment of FIG. 4, the through-housing 114, the blind housing116, the pin at an inner radial position 118, and the pin at an outerradial position 120 are coaxial and are aligned in a radial directionrelative to the annular flange 30. More specifically, according to thisembodiment, these elements extend in a substantially radial direction,oriented towards the geometric axis of rotation R. However, in analternative embodiment, said through-housing 114, blind housing 116, pinat an inner radial position 118, and pin at an outer radial position 120could also be oriented in a direction slightly inclined and forming anangle α with respect to a radial direction relative to the annularflange 30.

In the embodiment of FIG. 4, the blind housing 116 is flush with thethrough-housing 114, but there could also be a gap formed between theblind housing 116 and the through-housing 114 without this affecting thecontainment and handling of the container 20.

When the container 20 is in the initial locking position, as shown inFIG. 5 a, the pin at an inner radial position 118 has an internalfunctional portion for initial locking 118 _(INT) arranged in the blindhousing 116 of the removable cover 28 and an external functional portionfor initial locking 118 _(EXT) arranged in the through-housing 114 ofthe annular flange 30. Thus, the pin at an inner radial position 118prevents the relative movement of the removable cover 28 with respect tothe annular flange 30.

Moreover, in this same initial locking position, the pin at an outerradial position 120 is at least partially arranged in thethrough-housing 114 of the annular flange 30. In a first embodiment(shown in FIG. 5 a), the pin at an outer radial position 120 can thenhave a functional end portion at an outer radial position 122 that isnot within the through-housing 114. This facilitates access to thisfunctional end portion 122 by the stationary unlocking means 60 orlocking means 70. In a second embodiment (not shown), this pin at anouter radial position 120 may alternatively have a functional endportion at an outer radial position 122 which is flush with the outerend opening of the through-housing 114. Access to this functional endportion 122 by the stationary unlocking means 60 or locking means 70then remains relatively easy but the risk of inadvertently moving thepin at an outer radial position 120 is reduced. Finally, according to athird embodiment (not shown), said pin at an outer radial position 120may have a functional end portion at an outer radial position 122 whichis entirely housed within the through-housing 114. In this manner, it isvirtually impossible to manipulate the pin at an outer radial position120 without using a specific tool.

When the container 20 is in the intermediate unlocked position, as shownin FIG. 5 b, the pin at an inner radial position 118 is at leastpartially arranged within the blind housing 116 of the removable cover28 and is completely outside the through-housing 114 of the annularflange 30. In this manner, the pin at an inner radial position 118 nolonger prevents the relative movement of the annular flange 30 and theremovable cover 28 of the container 20.

In this intermediate unlocking position, the pin at an outer radialposition 120 is at least partially arranged in the through-housing 114of the annular flange 30 and is completely outside the blind housing 116of the removable cover 28. In this manner, the pin at an outer radialposition 120 has no more effect than the pin at an inner radial position118 on the relative movement of the removable cover 28 with respect tothe annular flange 30 which can therefore be separated to allow theaseptic transfer of biopharmaceutical products.

Similarly to the above, the functional end portion at an outer radialposition 122 of said pin at an outer radial position 120 may either becompletely outside the through-housing 114, or flush with the outer endopening of the through-housing 114, or be entirely housed within saidthrough-housing 114.

Finally, to place the container 20 in the final locking position, asshown in FIG. 5 c, it is first necessary to replace the removable cover28 against the annular flange 30 and then place the built-in functionalarrangement for locking/unlocking 112 in the appropriate position.

More particularly, in this position, the pin at an inner radial position118 is positioned entirely within the blind housing 116 of the removablecover 28, while the pin at an outer radial position 120 has an internalfunctional portion for final locking 120 _(INT) arranged in the blindhousing 116 of the removable cover 28 and an external functional portionfor final locking 120 _(EXT) arranged in the through-housing 114 of theannular flange 30. Therefore, the blind housing 116 of the removablecover 28 has a length sufficient to accommodate the pin at an innerradial position 118 on the one hand, and the internal functional portionfor final locking 120 _(INT) on the other hand. Thus, the pin at anouter radial position 120 prevents the relative movement of theremovable cover 28 with respect to the annular flange 30.

Again, the functional end portion 122 at an outer radial position ofsaid pin at an outer radial position 120 may then be completely outsidethe through-housing 114 in order to facilitate any subsequent reopeningof the container 20. Conversely, said functional end portion 122 at anouter radial position may be flush with the external end opening of thethrough-housing 114 or may be housed entirely within saidthrough-housing 114 to limit the subsequent risk of opening thecontainer 20.

Such use of pins at inner and outer radial positions 118, 120 to placethe container in the initial locking, intermediate unlocking, and finallocking positions makes it possible to have only one blind housing 116and through-housing 114 in the removable cover 28 and the annular flange30 per built-in functional arrangement for locking/unlocking 112, whichlimits the risk of contamination due to production defects. In addition,manipulation of the locking/unlocking means 110 is facilitated, as it issufficient to move the inner and outer pins 118, 120 in a singledirection in order to transition the container 20 successively from theinitial locking position to the intermediate unlocking position, andthen to the final locking position. The construction and operation ofthe leaktight joining device are thus simplified.

It should be noted that in the embodiment of FIG. 4, the pins at innerand outer radial positions 118, 120 have identical lengths, whichsimplifies the production and assembly of the pins at inner and outerradial positions 118, 120 on the container since it is then unnecessaryto distinguish the pins according to their dimensions. Alternatively,these pins at inner and outer radial positions 118, 120 could havedifferent lengths.

It should also be noted that the through-housing 114 and the pin at anouter radial position 120 have lengths such that, when the built-inlocking/unlocking means 110 are in the provisional unlocking position,the pin at an outer radial position 120 has a functional end portion 122at an outer radial position which is completely outside thethrough-housing 114. This facilitates the operation carried out by thestationary locking means 70 for transitioning the container 20 from theintermediate unlocking position to the final locking position becausethe pin at an outer radial position 120 is accessible without theradially movable pushing element 78 having to move all the way to theinside of the through-housing 114.

However, the lengths of the pin at an outer radial position 120 and ofthe through-housing 114 are such that, when the built-inlocking/unlocking means 110 are in the final locking position, said pinat an outer radial position 120 has a functional end portion 120 at anouter radial position that is housed within the through-housing. Whenthe container is placed in the final locking position, it then becomescomplex and impractical without a suitable gripping tool to grasp thepin at an outer radial position 120. This raises the level of securityrelating to the fluid-tightness of the container 20 in the final lockingposition.

It would also be possible to integrate complementary protection andwarning means—formed for example by complementary abutments or anysimilar element—on the pin at an outer radial position 120 and on thethrough-housing 114, preventing the removal of the pin at an outerradial position 120 from the housing 114 after the container 20 hastransitioned to the final locking position and causing the destructionof a portion of the annular flange 30 in the event of such removal.

Alternatively (not shown), it is also possible for the lengths of thepin at an outer radial position 120 and of the through-housing 114 to besuch that, when the built-in locking/unlocking means 110 are in thefinal locking position, said pin at an outer radial position 120 has afunctional external end at an outer radial position that is completelyoutside the through-housing.

Such an embodiment would, however, facilitate the removal of the pin atan outer radial position 120 from the through-housing 114 and wouldprovide a container that is reusable after being in the final lockingposition.

According to the embodiment of FIG. 4, the container 20 also includesbuilt-in isolation and protection means 124.

The built-in isolation and protection means 124 are arranged on an outerperipheral portion of the annular flange 30 so as prevent inadvertentmanipulation of the built-in locking/unlocking means supported by theannular flange 30.

In one embodiment, the built-in isolation and protection means 124include four built-in functional arrangements for isolation andprotection 126 placed around the four through-housings 114 so as toprevent inadvertent or deliberate manipulation of the pin at an outerradial position 120 when said pin is not fully inserted into thethrough-housing 118 in the annular flange 30.

Each built-in functional arrangement for isolation and protection 126 isbased on two lugs 128, arranged around or on either side of thethrough-housing 114. In this embodiment, the lugs 128 have radialdimensions such that, in the temporary locking position, the pin at anouter radial position 120 does not extend beyond the lugs 128constituting the isolation and protection means.

However, in an alternative or additional embodiment, the built-infunctional arrangement for isolation and protection 62 could be based ona bore formed in the annular flange 30, radially oriented and having adiameter greater than the diameter of the through-housing 114. Such anembodiment would prevent access to the outer pin 120 while maintainingthe space around this outer pin 120 in order to avoid complicating theoperation of moving said pin by the stationary locking means 60 andunlocking means 70.

It should be noted that in the embodiment of FIG. 4, the lugs 104forming the built-in temporary clamping means 102 and the lugs 128forming the built-in isolation and protection means 124 are the same.These lugs 104, 108 therefore have, on the one hand, a built-infunctional surface for axial clamping 56 ensuring the clamping of thecontainer against the peripheral wall 12 of the chamber 10, and on theother hand a shape which protects and isolates the outer pin 120 when itis only partially inserted into the through-housing 114. Such anembodiment can reduce production costs and simplify the annular flange30 by limiting the number of lugs to be created on the outer peripheraledge of the annular flange 30.

However, it would also be conceivable to use built-in temporary clampingmeans 102 and built-in isolation and protection means 124 that arestructurally and functionally independent of each other, for exampleusing some lugs 104 for the axial clamping and other different lugs forthe isolation and protection of the outer pin 120.

It should be noted that similarly to the above, the built-in temporaryclamping means 100 are arranged so as to index the position of thecontainer 20 relative to the other stationary means that are part of theleaktight joining device 40. This accumulation of functionalarrangements on the annular functional ring gear 42 allows completing amanipulation cycle of the container 20 with only a 1/n revolution of theannular functional ring gear 42. In the current case, the embodimentcomprises four distinct functional arrangements distributed evenlyaround the annular functional ring gear 42, but it would be possible toinclude less—one, two, or three—or to include more.

The implementation of the aseptic transfer method of the invention willnow be described in detail, with reference to FIG. 6.

This aseptic transfer method first consists of having a closed chamber10 as described above and supporting a leaktight joining device 40 ofthe invention. Then this aseptic transfer method consists of having acontainer 20 in the initial locking position as described above.

The aseptic transfer method next involves placing the container 20against the peripheral wall 12 of the chamber 10, introducing the lugs104 that are part of the built-in functional arrangements for temporaryclamping 102 through the insertion openings 58 that are part of thestationary temporary clamping means 50.

By doing so, the annular flange 30 of the container 20 comes intoposition against the peripheral wall 12 of the chamber 10 and theremovable cover 28—at least partially formed of ferrite—is sealinglyheld against the outer face of the removable door 18—at least partiallymagnetized.

The aseptic transfer method then consists of generating the clockwiserotation of the annular functional ring gear 42 so that the functionalring portions acting as clamp 54 are positioned facing the lugs 104forming the built-in temporary clamping means and trap these lugs 104between the peripheral wall 12 of the chamber 10 and the axiallyclamping functional surfaces 56.

The container 20 is thus held in position by the leaktight joiningdevice 40 against the circumferential wall 12 of the chamber 10.

The aseptic transfer method then consists of generating the clockwiserotation of the annular functional ring gear 42 to actuate thestationary unlocking means 60. More particularly, the clockwise rotationof this annular functional ring gear 42 generates a movement of theradially moveable pushing element 68 due to the change in radialposition of the roller 68 a in the guideway 66. The activation pin 68 bthen lowers and pushes the pin at an outer radial position 120 and thepin at an inner radial position 118 at the same time.

Following this operation, the pin at an inner radial position 118 isarranged in the blind housing 116 of the removable cover 28 and iscompletely outside the through-housing 114 in the annular flange 30, andthe pin at an outer radial position 120 is arranged in thethrough-housing 114 in the annular flange 30 and is completely outsidethe blind housing 116 in the removable cover 28. The container 20 isthus in the intermediate unlocking position and the relative movement ofthe removable cover 28 with respect to the annular flange 30 ispossible.

The aseptic transfer method also consists of, simultaneous with orsuccessive to the preceding step, generating the clockwise rotation ofthe annular functional ring gear 42 to actuate the stationaryretaining/release means 80 in order to release the removable door 18 ofthe chamber 10.

To this end, the functional ring portions forming gear teeth 84—whichare rotationally driven with the annular functional ring gear 42—meshwith the drive shaft 86 and therefore with the blocking member 88 sothat the latter no longer covers the outer face of the removable door 18of the chamber 10. The removable door 18 can then be freely manipulated.

The aseptic transfer method then consists of causing the stationaryoperating means 90 to drive the removable door 18 of the chamber 10 andthe removable cover of the container so as to free the annular openings16, 26 of the chamber 10 and of the container 20.

To do this, the stationary operating means 90—which can be actuated bythe annular functional ring gear 42 or by a motor controlled by theposition of the annular functional ring gear 42—first drive theremovable door 18 of the chamber 10 in a horizontal translation and thenin a rotation about a horizontal axis,.

As the container 20 is in the intermediate unlocking position, theremovable cover 28 can be moved relative to the annular flange 30 andcan follow the movements of the removable door 18 of the chamber 10 dueto the magnetic force connecting them together. Thus, the chamber 10 andthe container 20 are open to each other while being hermeticallyisolated from the outside environment.

The aseptic transfer of biopharmaceutical products between the container20 and the chamber 10 can then occur.

The aseptic transfer method then consists of again driving thestationary operating means 90 so that the annular openings 16, 26 of thechamber 10 and of the container 20 are once again sealed closed.

As above, the stationary operating means 90 drive the removable door 18of the chamber 10 and the removable cover of the container 20 in arotation about a horizontal axis and then in a horizontal translation toreturn them to the same position as before.

The chamber 10 is then once again sealed by the removable door 18,relative to the outside and to the container 10. Symmetrically, thecontainer 20 is sealed by the removable cover, relative to the outsideand to the chamber 10.

The aseptic transfer method then consists of generating the clockwiserotation of the annular functional ring gear 42 to actuate thestationary retention/release means 80 in order to prevent movement ofthe removable door 18 of the chamber 10.

To this end, the functional ring portions forming gear teeth 84—whichrotate with the annular functional ring gear 42—engage the drive shaft86 and thus the blocking member 88, so that said blocking member onceagain covers the outer face of the removable door 18 of the chamber 10.The removable door 18 can then no longer be freely manipulated.

The aseptic transfer method consists, simultaneously with or successiveto the previous step, of generating the clockwise rotation of theannular functional ring gear 42 in order to actuate the stationarylocking means 70. More particularly, the clockwise rotation of thisannular functional ring gear 42 generates a movement of the radiallymovable pushing element 78 due to the change of radial position of theroller 68 a in the guideway 76. The activation pin 68 b then lowers andpushes against the pin at an outer radial position 120 and the pin at aninner radial position 118 at the same time.

Following this operation, the pin at an inner radial position 118 isarranged within the blind housing 116 of the removable cover 28 whilethe pin at an outer radial position 120 has an internal functionalportion for final locking 120 _(INT) arranged within the blind housing116 of the removable cover 28 and an outer functional portion for finallocking 120 _(EXT) arranged within the through-housing 114 in theannular flange 30. Relative movement of the removable cover 28 withrespect to the annular flange 30 is therefore impossible and thecontainer is then in the final locking position.

The aseptic transfer method then consists of generating the clockwiserotation of the annular functional ring gear 42 in order for thefunctional ring portions acting as temporary clamp 54 to be positionedso the insertion openings 58 are facing the lugs 104 forming thebuilt-in temporary clamping means and free them.

The container 20 in the final locking position can thus be freelyremoved from the leaktight sealing device 40.

1. A container (20) specially intended for the transport and the aseptictransfer of a biopharmaceutical product to or from a closed chamber (10)equipped with a leaktight joining device (40), comprising: an annularflange (30) delimiting an opening (26); a removable cover (28) adaptedfor sealing the opening (26) of the annular flange (30); built-in meansfor locking/unlocking (110) the removable cover (28) on the annularflange (30); and a peripheral envelope (22) integral with the annularflange (30) and delimiting an enclosed inside space (24) adapted forreceiving products belonging to the biopharmaceutical field; wherein thebuilt-in locking/unlocking means (110) comprise at least one built-infunctional locking/unlocking arrangement (112) formed, on the one hand,by a through-housing (114) formed in the annular flange (30) and a blindhousing (116) formed in the removable cover (28) and in the extension ofthe through-housing (114) when the removable cover (28) seals theopening of the annular flange (30), and, on the other hand, by a pin atan inner radial position (118) and a pin at an outer radial position(120) which can be introduced and moved within the blind housing (116)of the removable cover (28) and the through-housing (114) of the annularflange (30); the container (20) being able to be in an initial lockingposition where, on the one hand, the pin at an inner radial position(118) has an internal functional portion for initial locking (118_(INT)) arranged in the blind housing (116) of the removable cover (28)and an external functional portion for initial locking (118 _(EXT))arranged in the through-housing (114) of the annular flange (30) so asto prevent the relative movement of the removable cover (28) withrespect to the annular flange (30), and, on the other hand, the pin atan outer radial position (120) is at least partially arranged in thethrough-housing (114) of the annular flange (30); the container (20)being able to be in an intermediate unlocking position in which, on theone hand, the pin at an inner radial position (118) is at leastpartially arranged in the blind housing (116) of the removable cover(28) and is completely outside the through-housing (114) of the annularflange (30) and, on the other hand, the pin at an outer radial position(120) is at least partially arranged in the through-housing (114) of theannular flange (30) and is completely outside the blind housing (116) ofthe removable cover (28) so as to allow the relative movement of theremovable cover (28) with respect to the annular flange (30);characterized in that the container (20) is able to be in a finallocking position where, on the one hand, the pin at an inner radialposition (118) is arranged in the blind housing (116) of the removablecover (28), and, on the other hand, the pin at an outer radial position(120) has an internal functional portion for final locking (120 _(INT))arranged in the blind housing (116) of the removable cover (28) and anexternal functional portion for final locking (120 _(EXT)) arranged inthe through-housing (114) of the annular flange (30) so as to preventthe relative movement of the removable cover (28) with respect to theannular flange (30).
 2. Container (20) according to claim 1, wherein thethrough-housing (114) and the pin at an outer radial position (120) havelengths such that, when the built-in locking/unlocking means (110) arein the initial locking position, said pin at an outer radial position(120) has a functional end portion at the outer radial position (122)which is either completely outside the through-housing (114), or ishoused inside the through-housing (114), or is flush with the outer endopening of the through-housing (114).
 3. Container (20) according toclaim 1, wherein the through-housing (114) and the pin at an outerradial position (120) have lengths such that, when the built-inlocking/unlocking means (110) are in the intermediate unlockingposition, said pin at an outer radial position (120) has a functionalend portion at the outer radial position (122) which is eithercompletely outside the through-housing (114), or is housed inside thethrough-housing (114), or is flush with the outer end opening of thethrough-housing (114).
 4. Container (20) according to claim 1, whereinthe through-housing (114) and the pin at an outer radial position (120)have lengths such that, when the built-in locking/unlocking means (110)are in the final locking position, said pin at an outer radial position(120) has a functional end portion at the outer radial position (122)which is either completely outside the through-housing (114), or ishoused inside the through-housing (114), or is flush with the outer endopening of the through-housing (114).
 5. Container (20) according toclaim 1, wherein the pin at an inner radial position (118) and pin at anouter radial position (120) have substantially identical lengths. 6.Container (20) according to claim 1, wherein the through-housing (114),the blind housing (116), the pin at an inner radial position (118), andthe pin at an outer radial position (120) are coaxial and oriented in aradial direction relative to the annular flange (30).
 7. Container (20)according to claim 1, wherein the through-housing (114), the blindhousing (116), the pin at an inner radial position, and the pin at anouter radial position (120) are coaxial and oriented in a directionforming an angle α with respect to a radial direction relative to theannular flange (30).
 8. Container (20) according to claim 1, comprisingbuilt-in isolation and protection means (124) arranged on an outerperipheral edge of the annular flange (30) so as to obstruct aninadvertent manipulation of the built-in locking/unlocking means (110).9. Container (20) according to claim 8, wherein the built-in isolationand protection means (124) comprise at least one built-in functionalarrangement for isolation and protection (126), provided around thethrough-housing (114) so as to obstruct an advertent manipulation of thepin at an outer radial position (120).
 10. Container (20) according toclaim 9, wherein the built-in functional arrangement for isolation andprotection (126) has radial dimensions such that, in a temporary lockingposition, the pin at an outer radial position (120) does not extendbeyond said isolation and protection means (124).
 11. Container (20)according to claim 9, wherein the built-in arrangement for functionalisolation and protection (126) comprises at least one lug (128),preferably two lugs (128), arranged around the through-housing (114) ofthe annular flange (30).
 12. Container (20) according to claim 9,wherein the isolation and protection arrangement (126) comprises a boreformed in the annular flange (30) and having a diameter greater than thediameter of the through-housing (114).
 13. Container (20) according toclaim 1, comprising built-in temporary clamping means (100) arranged onan outer peripheral edge of the annular flange (30) so as to allowtemporarily clamping the container (20) by preventing axial movement onthe closed chamber (10) via actuation of the leaktight joining device(40).
 14. Container (20) according to claim 13, wherein the built-intemporary clamping means (100) comprise at least one built-in functionalarrangement for temporary clamping (102) formed by at least one lug(104), preferably two lugs (104) having a built-in functional surfacefor axial clamping (106) adapted to abut against a stationary functionalsurface for axial clamping (56), of the leaktight joining device (40),so as to prevent axial movement of the container (20) relative to thechamber (10).
 15. Container (20) according to claim 14 comprisingbuilt-in isolation and protection means (124) arranged on an outerperipheral edge of the annular flange (30) so as to obstruct aninadvertent manipulation of the built-in locking/unlocking means (110),wherein the built-in temporary clamping means (100) are at least partlyformed by the isolation and protection means (124).
 16. Container (20)according to claim 15, wherein the built-in functional arrangement fortemporary clamping (102) and the built-in functional arrangement forisolation and protection (126) are formed by at least one common lug(104, 128), and preferably two common lugs (104, 128).
 17. Container(20) according to claim 1, wherein the built-in locking/unlocking means(110) comprise n built-in functional arrangements for locking/unlocking(112), regularly distributed around the annular flange (30) and theremovable cover (28), with n greater than or equal to
 1. 18. Container(20) according to claim 17, wherein the built-in isolation andprotection means (124) comprise n built-in functional arrangements forisolation and protection (126), regularly distributed around the annularflange (30) and indexed relative to the n built-in functionalarrangements for locking/unlocking (112).
 19. Container (20) accordingto claim 14, wherein the built-in temporary clamping means (100)comprise m built-in functional arrangements for temporary clamping(102), regularly distributed around the annular flange (30), with mgreater than or equal to
 1. 20. Container (20) according to claim 19,wherein the built-in functional arrangement for temporary clamping (102)and the built-in functional arrangement for isolation and protection(126) are formed by at least one common lug (104, 128), and n is equalto m and the built-in functional arrangements for temporary clamping(102) are indexed relative to the built-in functional arrangements forlocking/unlocking (112).
 21. Container (20) according to claim 1,wherein the container (20) is disposable.
 22. Assembly comprising achamber (10), a leaktight joining device (40), and a container (20)according to claim 1, for performing the aseptic transfer of abiopharmaceutical product between the chamber (10) and the container(20).
 23. Assembly according to claim 22, wherein the chamber (10)comprises a peripheral wall in which is arranged an opening sealed by aremovable door, and wherein the leaktight joining device (40) comprises:stationary temporary clamping means (50) able to keep the container (20)clamped against the chamber (10) so that the removable cover (28) ofsaid container (20) is sealingly held against the removable door (18) ofsaid chamber (10); stationary unlocking means (60) able to cause thecontainer (20) to transition from an initial locking position where theremovable cover (28) seals the container (20) to an intermediateunlocking position where the removable cover (28) is disengaged from thecontainer (20) and is sealingly held against the door of the chamber(10) so as to ensure an aseptic communication between said container(20) and said chamber (10); stationary locking means (70) able to causethe container (20) to transition from the intermediate unlockingposition to a final locking position where said removable cover (28)once again seals the container (20); a annular functional ring gear (42)able to rotate about a geometric axis of rotation (R) so as to actuatethe stationary unlocking means (60) and the stationary locking means(70) of the container (20); the stationary temporary clamping means(50), the stationary unlocking means (60), and the stationary lockingmeans (70) being mechanically linked to the annular functional ring gear(42) so that the one-way rotation of said annular functional ring gear(42) about the geometric axis of rotation (R) successively causes theactuation of the stationary temporary clamping means (50) to hold thecontainer (20) in position against the chamber (10), then the actuationof the stationary unlocking means (60) which causes the container (20)to transition to the intermediate unlocking position, then the actuationof the stationary locking means (70) of the container (20) which causesthe container (20) to transition to the final locking position, and theactuation of the stationary temporary clamping means (50) of thecontainer (20) which results in the release of the container (20). 24.Method for aseptic transfer, intended for the aseptic transfer of abiopharmaceutical product between a container (20) and a chamber (10)which are part of an assembly according to claim 22, characterized inthat it comprises successive steps consisting of: having available thechamber (10), the leaktight joining device (40), and the container (20);positioning the container (20) against the peripheral wall (12) of thechamber (10); generating an axial clamping of the annular flange (30) ofthe container (20) against the peripheral wall (12) of the chamber (10)by one-way rotation of the annular functional ring gear (42); generatingthe transition of the container (20) from the initial locking positionto the intermediate unlocking position by one-way rotation of theannular functional ring gear (42), causing the displacement of the pinsat the inner (118) and outer (120) radial positions within thethrough-housing (114) and blind housing (116); simultaneously openingthe removable door (18) of the chamber (10) and the removable cover (28)of the container (20), the removable cover (28) being sealingly attachedagainst the removable door (18); aseptically transferring one or morebiopharmaceutical product(s) between the container (20) and the chamber(10); simultaneously closing the removable door (18) of the chamber (10)and the removable cover (28) of the container (20), the removable cover(28) being sealingly attached against the removable door (18);generating the transition of the container (20) from the intermediateunlocking position to the final locking position by one-way rotation ofthe annular functional ring gear (42) which causes movement of the pinsat the inner (118) and outer (120) radial positions within thethrough-housing (114) and blind housing (116); generating the axialunclamping of the annular flange (30) of the container (20) relative tothe peripheral wall (12) of the chamber (10) by one-way rotation of theannular functional ring gear (42).